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Cell Growth & Differentiation, Vol 8, Issue 8 871-879, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Treatment of U937 cells with bufalin induces the translocation of casein kinase 2 and modulates the activity of topoisomerase II prior to the induction of apoptosis

M Watabe, S Nakajo, T Yoshida, Y Kuroiwa and K Nakaya
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.

The treatment of human leukemia U937 cells with 10(-8) M bufalin in the absence of serum resulted in the immediate translocation of casein kinase 2 (CK 2) from the cytoplasm to the nucleus, as determined by confocal laser-scanning microscopy. Concomitantly, the activity of topoisomerase (topo) II, as determined by monitoring activities specific to this enzyme such as DNA relaxation, DNA decatenation, and topo II-mediated DNA cleavage, was enhanced. The activity reached a maximum after 3 h and then decreased markedly after treatment with bufalin for 9 h. The amount of a complex of CK 2 and topo IIalpha in U937 cells was estimated by immunoprecipitation with antibodies raised against subunits of CK 2 and against topo IIalpha. The amount increased just after the start of treatment with bufalin and reached a maximum at 6 h. The results suggest that the topo IIalpha in the complex might have been phosphorylated by the translocated CK 2 and that the topo activity was stimulated by such phosphorylation. Apoptotic U937 cells with fragmented nuclei were observed between 9 and 12 h after the start of treatment using 10(-8) M bufalin. Therefore, it appears that the bufalin signal was transmitted to the nucleus by the translocation of CK 2, which formed a complex with topo IIalpha and modulated the activity of this enzyme, leading to the induction of apoptosis.


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.